ATYPICAL MYCOBACTERIAL INFECTION - NTM IN ORTHOPAEDICS
Non-Tuberculous Mycobacteria | M. marinum Classic | Rice Body Tenosynovitis | Prolonged Multi-Drug Therapy
CLASSIFICATION BY GROWTH RATE (RUNYON)
Critical Must-Knows
- High index of suspicion in chronic culture-negative infection with granulomatous histology
- M. marinum is classic for hand tenosynovitis after aquarium or fish exposure (fish tank granuloma)
- Rice bodies in tenosynovitis are pathognomonic - fibrin deposits within tendon sheath
- AFB culture takes 2-6 weeks - must specifically request mycobacterial culture
- Surgical debridement PLUS prolonged antibiotics (3-6 months) is standard treatment
Examiner's Pearls
- "M. marinum optimal growth at 30-32C (cooler extremities) - incubate at lower temperature
- "Rapidly growing mycobacteria cause post-surgical wound infections (M. fortuitum, M. abscessus)
- "MAC disseminated infection occurs in severely immunocompromised (CD4 count less than 50)
- "Clarithromycin is the cornerstone of most NTM regimens - never use as monotherapy
Critical NTM Exam Points - High Index of Suspicion Required
When to Suspect NTM
Think NTM in: chronic indolent tenosynovitis, culture-negative joint infection, chronic wound with granulomas, atypical presentation not responding to standard antibiotics, immunocompromised host, aquarium/fish exposure, post-procedural wound infection.
M. marinum - Fish Tank Granuloma
Classic presentation: Aquarium enthusiast, fish handler, or swimming pool exposure presenting with nodular hand/wrist tenosynovitis weeks to months later. May have sporotrichoid spread (ascending nodules along lymphatics). Optimal growth at 30-32C - cool incubation required.
Rice Body Tenosynovitis
Pathognomonic finding: Multiple white rice-grain sized bodies within tendon sheath. Fibrin deposits from chronic inflammation. Classic for NTM but also seen in TB and rheumatoid arthritis. Requires synovectomy and prolonged antibiotics for cure.
Culture and Diagnosis
AFB culture takes 2-6 weeks - must specifically request. Standard bacterial cultures negative. Histology shows granulomas with or without caseation. PCR allows rapid species identification. AFB smear often negative (low organism burden).
Non-Tuberculous Mycobacteria - Key Organisms in Orthopaedics
| Organism | Source/Exposure | Clinical Presentation | Treatment Approach |
|---|---|---|---|
| M. marinum | Aquarium, fish, swimming pools | Hand/wrist tenosynovitis, sporotrichoid spread | Clarithromycin + rifampicin OR ethambutol, 3-6 months |
| M. avium complex (MAC) | Environmental (soil, water) | Disseminated in AIDS, pulmonary in elderly, rare joint infection | Clarithromycin + ethambutol +/- rifampicin, 12+ months |
| M. kansasii | Water supply, geographic clusters | Pulmonary TB-like, tenosynovitis, osteomyelitis | Isoniazid + rifampicin + ethambutol, 12-18 months |
| M. fortuitum | Soil, water, surgical contamination | Post-surgical wound infection, catheter infection | Clarithromycin + amikacin +/- fluoroquinolone, 4-6 months |
| M. chelonae | Soil, water, contaminated solutions | Skin/soft tissue, post-injection abscess | Clarithromycin-based, avoid aminoglycosides (resistant) |
| M. abscessus | Water, contaminated equipment | Post-surgical, skin/soft tissue, most resistant rapid grower | Clarithromycin + amikacin + cefoxitin, most difficult to treat |
| M. ulcerans | Tropical/endemic areas, Australia | Buruli ulcer - painless progressive skin ulcer | Rifampicin + clarithromycin 8 weeks, surgery for large lesions |
FISH TANKNTM Suspicion Triggers
Memory Hook:FISH TANK exposure should trigger suspicion for atypical mycobacteria - always ask about aquarium and water exposure!
SLOW vs FASTNTM Growth Rate Classification
Memory Hook:SLOW growers from environment, FAST growers cause healthcare infections - both need multi-drug therapy!
AQUARIUMM. marinum Features
Memory Hook:Think AQUARIUM when you see chronic hand tenosynovitis - M. marinum is the fish tank granuloma!
COMBONTM Treatment Principles
Memory Hook:COMBO therapy is mandatory - clarithromycin plus additional agents for prolonged duration with surgical debridement!
Overview and Epidemiology
Why This Topic Matters
Atypical mycobacterial infections are commonly missed due to their indolent nature and the need for specific culture requests. In the exam, NTM should be considered in any chronic culture-negative tenosynovitis or wound, especially with exposure history. The key learning points are recognition, appropriate investigation, and understanding of prolonged multi-drug therapy.
Epidemiology
- Increasing incidence worldwide over past decades
- Environmental organisms - soil, water, not human-to-human transmission
- M. marinum most common NTM causing hand infections
- MAC most common NTM overall in immunocompromised
- Rapid growers increasingly recognized in surgical site infections
- Risk factors: Immunosuppression, aquatic exposure, fish handling, tropical travel
Orthopaedic Relevance
- Tenosynovitis - especially hand and wrist flexor sheaths
- Septic arthritis - chronic, indolent presentation
- Osteomyelitis - less common, usually adjacent to soft tissue
- Post-surgical infection - rapid growers after procedures
- Bursitis - olecranon, prepatellar
- Often presents as culture-negative chronic infection
Definition
Non-Tuberculous Mycobacteria (NTM), also known as atypical mycobacteria or mycobacteria other than tuberculosis (MOTT), are a diverse group of acid-fast bacilli found ubiquitously in the environment. Unlike M. tuberculosis, they are not obligate human pathogens and do not require isolation precautions. They cause a spectrum of disease from localized skin and soft tissue infections to disseminated disease in immunocompromised hosts.
Commonly Missed Diagnosis
NTM infections are frequently missed because standard bacterial cultures do not detect them, and AFB cultures must be specifically requested. Always consider NTM in chronic indolent infections, especially in the hand, that fail standard antibiotic therapy and have negative routine cultures.
Microbiology
Runyon Classification of NTM
The traditional classification is based on growth rate and pigment production, though molecular identification is now standard.
Runyon Classification of NTM
| Group | Growth Rate | Pigment Production | Key Species |
|---|---|---|---|
| Group I - Photochromogens | Slow (more than 7 days) | Yellow pigment in light only | M. marinum, M. kansasii |
| Group II - Scotochromogens | Slow (more than 7 days) | Pigmented in dark and light | M. scrofulaceum, M. gordonae |
| Group III - Nonchromogens | Slow (more than 7 days) | No pigment production | M. avium complex, M. ulcerans |
| Group IV - Rapid growers | Fast (less than 7 days) | Variable | M. fortuitum, M. chelonae, M. abscessus |
Pigment Production
Photochromogens (M. marinum, M. kansasii) produce yellow-orange pigment only when exposed to light. Scotochromogens produce pigment in both light and dark. Nonchromogens (MAC) produce no pigment. This traditional classification is still tested but molecular methods now provide definitive identification.
The classification helps predict clinical syndromes and guides initial therapy.
Clinical Presentation
NTM Tenosynovitis - Classic Presentation
Flexor tenosynovitis of the hand and wrist is the most common orthopaedic presentation of NTM infection, particularly M. marinum.
Clinical Features
- Gradual onset over weeks to months
- Swelling along flexor tendon sheath
- Carpal tunnel syndrome from synovial thickening
- Variable pain - often less than expected for degree of swelling
- Finger triggering may be present
- Range of motion progressively limited
- Usually single digit or carpal tunnel region
- May extend to palm (horse-shoe abscess)
Rice Body Formation
- Pathognomonic finding - white rice-grain sized bodies
- Represent fibrin deposits from chronic synovial inflammation
- Found within tendon sheath at surgery
- Classic for NTM but also seen in:
- Tuberculosis
- Rheumatoid arthritis
- Seronegative arthritis
- Require debridement/synovectomy for cure
Rice Bodies in the Exam
When you encounter rice bodies at surgery for chronic tenosynovitis, always send tissue for AFB culture and TB culture in addition to routine bacterial culture and histology. The differential includes NTM (especially M. marinum), TB, and rheumatoid disease. Rice bodies are fibrin deposits, not the organisms themselves.
The classic triad is chronic tenosynovitis, rice bodies, and granulomatous histology - think mycobacteria.
Diagnosis
Microbiological Diagnosis
Diagnostic Tests for NTM
| Test | Utility | Limitations |
|---|---|---|
| AFB smear (Ziehl-Neelsen) | Rapid, same-day result if positive | Low sensitivity (10-40%), paucibacillary infections often negative |
| AFB culture | Gold standard for diagnosis, allows susceptibility testing | Takes 2-6 weeks, must specifically request, temperature-dependent for M. marinum |
| PCR/NAAT | Rapid species identification, high sensitivity | Not available everywhere, cannot determine susceptibility |
| 16S rRNA sequencing | Definitive species identification | Takes days, reference laboratory needed |
| Histopathology | Granulomatous inflammation supports diagnosis | Non-specific, cannot identify species, may miss early infection |
Must Request AFB Culture
AFB cultures are NOT performed unless specifically requested. In any chronic culture-negative musculoskeletal infection, always request: 1) AFB culture and smear, 2) Fungal culture, 3) Extended bacterial culture. For suspected M. marinum, request incubation at 30-32C.
Multiple tissue samples increase diagnostic yield.
Management
Management Principles
Surgical Debridement
- Required for most NTM musculoskeletal infections
- Tenosynovectomy for flexor sheath involvement
- Debridement of infected/necrotic tissue
- Remove rice bodies and thickened synovium
- Obtain multiple tissue samples for culture
- May require staged procedures for extensive disease
Prolonged Antimicrobial Therapy
- Always multi-drug regimens (prevents resistance)
- Duration 3-6 months minimum for skin/soft tissue
- 6-12+ months for bone/joint involvement
- Clarithromycin is cornerstone of most regimens
- Susceptibility testing guides specific choices
- Monitor for drug toxicity (hepatic, auditory, visual)
Never Monotherapy
Mycobacterial infections must NEVER be treated with single-agent therapy. Resistance develops rapidly with monotherapy. Always use combination regimens with at least 2-3 active agents based on species identification and susceptibility testing.
Combined surgical debridement and prolonged multi-drug therapy is the standard of care.
Complications
Complications of NTM Infection
| Complication | Cause | Prevention/Management |
|---|---|---|
| Treatment failure/relapse | Inadequate duration, non-compliance, drug resistance | Prolonged therapy, compliance support, susceptibility-guided treatment |
| Tendon rupture | Chronic tenosynovitis, steroid injection (misdiagnosis) | Avoid steroids if infection suspected, surgical debridement |
| Carpal tunnel syndrome | Synovial thickening, compression of median nerve | Carpal tunnel release at time of synovectomy |
| Spread to adjacent structures | Delayed diagnosis, inadequate debridement | Early diagnosis, thorough surgical debridement |
| Joint destruction | Chronic septic arthritis | Early treatment, surgical intervention |
| Drug toxicity | Prolonged multi-drug therapy | Monitor LFTs (rifampicin), visual acuity (ethambutol), hearing (aminoglycosides) |
| Chronic sinus tract | Inadequate debridement, resistant organism | Radical debridement, revision surgery |
Steroid Injection Disaster
If tenosynovitis is misdiagnosed as De Quervain's or trigger finger and treated with corticosteroid injection, NTM infection may spread dramatically. Steroids suppress local immunity and allow uncontrolled bacterial proliferation. Always consider infection in atypical presentations before injecting steroids.
Evidence Base
M. marinum Tenosynovitis Treatment Outcomes
- Series of 63 M. marinum infection cases treated at referral center
- Clarithromycin-containing regimens had 85% cure rate
- Mean treatment duration 3.5 months for cure
- Surgical debridement required in 50% of cases
- Delayed diagnosis (more than 2 months) associated with need for surgery
NTM Species Distribution in Musculoskeletal Infections
- M. marinum accounts for 70-80% of NTM hand infections
- Rapidly growing mycobacteria increasing in surgical site infections
- M. abscessus is most resistant rapid grower with worst outcomes
- AFB smear sensitivity only 10-40% in NTM infections
- Molecular methods significantly faster for species identification
Rice Bodies in Tenosynovitis - Etiology and Management
- Rice bodies found in 17 cases of tenosynovitis over 10 years
- Mycobacterial infection (TB and NTM) in 35% of cases
- Rheumatoid arthritis in 41% of cases
- Seronegative inflammatory arthritis in 24%
- All cases required surgical synovectomy for definitive diagnosis
Treatment of Rapidly Growing Mycobacteria
- M. abscessus has worst outcomes of rapid growers - only 30-50% cure rate
- Inducible macrolide resistance (erm gene) present in majority of M. abscessus
- Initial IV therapy with amikacin + cefoxitin + clarithromycin recommended
- M. fortuitum most susceptible - often responds to oral therapy alone
- Surgical debridement essential for implant-associated infections
Optimal Culture Conditions for M. marinum
- M. marinum grows optimally at 30-32C, not 37C
- Standard 37C incubation may result in false-negative cultures
- Growth visible in 2-4 weeks at optimal temperature
- PCR can detect M. marinum in 24-48 hours
- Laboratory must be informed of clinical suspicion for appropriate incubation
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
Scenario 1: Chronic Flexor Tenosynovitis
"A 45-year-old aquarium shop owner presents with 3 months of progressive swelling and stiffness of the right index and middle fingers. He has difficulty making a fist. Previous treatment with oral flucloxacillin and then augmentin for 'infection' showed no improvement. Routine bacterial cultures have been negative. Examination shows swelling along the flexor tendons of digits 2-3 extending to the palm, reduced AROM, and positive Tinel's over the carpal tunnel. How would you approach this case?"
Scenario 2: Post-Surgical Wound Infection
"A 58-year-old woman with type 2 diabetes had knee arthroscopy for degenerative meniscal tear 6 weeks ago. She now presents with persistent wound discharge from the portal sites. She received two courses of oral antibiotics (cephalexin, then augmentin) from her GP with no improvement. Swabs have grown 'skin flora' only. The wounds show minimal erythema but have serous discharge. Inflammatory markers are mildly elevated (CRP 28). What are your differential diagnoses and management plan?"
Scenario 3: Culture-Negative Septic Arthritis
"A 62-year-old man presents with 8 weeks of progressive right wrist pain and swelling. He is immunocompetent with no significant medical history. He had a cortisone injection by his GP 3 months ago for presumed 'arthritis' which gave temporary relief. Joint aspiration shows WCC 18,000 with 75% neutrophils, but Gram stain is negative and cultures show no growth at 5 days. CRP is 35. X-ray shows periarticular osteopenia. How would you proceed?"
Australian Context
Epidemiology in Australia
Non-tuberculous mycobacterial infections are increasingly recognized in Australia, with several species having particular relevance to the Australian setting. The incidence of NTM disease has increased over recent decades, likely due to improved recognition, an aging population, and increased use of immunosuppressive therapies.
M. ulcerans causing Buruli ulcer is endemic in coastal Victoria (Bellarine Peninsula, Mornington Peninsula) and tropical Queensland. This should be considered in patients from endemic areas presenting with painless progressive skin ulceration. The recommended treatment per Australian guidelines is rifampicin plus clarithromycin for 8 weeks, with surgery reserved for large or complicated lesions.
Notification and Laboratory Services
NTM infections are not notifiable diseases in Australia (unlike tuberculosis), but laboratory reporting varies by state. State reference laboratories (VIDRL in Victoria, Pathology Queensland, etc.) provide mycobacterial culture and susceptibility testing with typical turnaround times of 2-6 weeks for slow growers. Molecular identification services including PCR and 16S rRNA sequencing are available through reference laboratories for rapid species identification when clinically needed.
Treatment Access
First-line antibiotics for NTM including clarithromycin, rifampicin, and ethambutol are available through the PBS for treatment of mycobacterial infections. Specialist infectious diseases consultation is recommended for complex NTM infections, particularly those involving M. abscessus or cases requiring IV therapy. Hospital-in-the-home (HITH) services may be utilized for prolonged IV antibiotic therapy when required for severe rapid-grower infections. Australian Therapeutic Guidelines (eTG) provides recommendations for NTM treatment aligned with international consensus.
Atypical Mycobacterial Infection
High-Yield Exam Summary
When to Suspect NTM
- •Chronic indolent tenosynovitis/arthritis not responding to standard antibiotics
- •Culture-negative infection with granulomatous histology
- •Aquarium, fish, or water exposure + hand/wrist infection
- •Rice bodies found at surgery
- •Post-surgical wound infection 3-6 weeks after procedure (rapid growers)
- •Immunocompromised host with atypical presentation
Key Organisms and Associations
- •M. marinum: Aquarium, fish tank, swimming pool - hand tenosynovitis, sporotrichoid spread
- •MAC: Disseminated in AIDS (CD4 less than 50), pulmonary in elderly
- •M. kansasii: TB-like, responds to rifampicin-based regimens
- •M. fortuitum: Post-surgical wounds, most susceptible rapid grower
- •M. chelonae: Post-injection abscess, aminoglycoside-resistant
- •M. abscessus: Post-surgical, most resistant, inducible macrolide resistance
Diagnosis Essentials
- •AFB culture takes 2-6 weeks - must specifically request
- •M. marinum requires 30-32C incubation (not 37C)
- •AFB smear often negative (low organism burden)
- •Histology: granulomas with or without caseation
- •PCR for rapid species identification if available
- •Multiple tissue samples (4-6) increase yield
Treatment Principles
- •NEVER monotherapy - always multi-drug regimens
- •Clarithromycin is cornerstone of most regimens
- •Surgical debridement usually required
- •Duration: 3-6 months skin/soft tissue, 6-12+ months bone/joint
- •Susceptibility testing guides therapy especially for rapid growers
- •Monitor toxicity: LFTs (rifampicin), vision (ethambutol), hearing (aminoglycosides)
M. marinum Specifics
- •Classic: aquarium exposure + chronic hand tenosynovitis + negative routine cultures
- •Incubation 2-4 weeks (up to 9 months)
- •Optimal growth at 30-32C - specify on culture request
- •Treatment: clarithromycin + rifampicin for 3-6 months
- •Tenosynovectomy + carpal tunnel release if CTS
- •Continue treatment 1-2 months after clinical resolution
Viva Red Flags
- •Steroid injection for presumed inflammatory tenosynovitis - will worsen NTM
- •Stopping antibiotics early based on symptom improvement
- •Not requesting AFB culture specifically
- •Using single-agent therapy
- •Missing inducible macrolide resistance in M. abscessus
- •Forgetting surgical debridement is usually required
References
-
Aubry A, Chosidow O, Caumes E, et al. Sixty-three cases of Mycobacterium marinum infection: clinical features, treatment, and antibiotic susceptibility of causative isolates. Arch Intern Med. 2002;162(15):1746-52.
-
Piersimoni C, Scarparo C. Extrapulmonary infections associated with nontuberculous mycobacteria in immunocompetent persons. Emerg Infect Dis. 2009;15(9):1351-58.
-
Wallace RJ Jr, Brown-Elliott BA, McNulty S, et al. Macrolide/azalide therapy for nodular/bronchiectatic Mycobacterium avium complex lung disease. Chest. 2014;146(2):276-282.
-
Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175(4):367-416.
-
Lewis FM, Marsh BJ, von Reyn CF. Fish tank exposure and cutaneous infections due to Mycobacterium marinum: tuberculin skin testing, treatment, and prevention. Clin Infect Dis. 2003;37(3):390-7.
-
Jernigan JA, Farr BM. Incubation period and sources of exposure for cutaneous Mycobacterium marinum infection. Clin Infect Dis. 2000;31(2):439-43.
-
Gonzalez-Santiago TM, Drage LA. Nontuberculous mycobacteria: skin and soft tissue infections. Dermatol Clin. 2015;33(3):563-77.
-
Tortoli E. Clinical manifestations of nontuberculous mycobacteria infections. Clin Microbiol Infect. 2009;15(10):906-10.
-
Wongworawat MD, Holtom PD, Learch TJ, et al. Clinical significance of rice bodies in recurrent tenosynovitis. J Hand Surg Am. 2005;30(2):302-7.
-
Thomson RM, Armstrong JG, Looke DF. Gastroesophageal reflux disease, acid suppression, and Mycobacterium avium complex pulmonary disease. Chest. 2007;131(4):1166-72.